Current interest in human tissue repair has prompted the development of biomaterial scaffolds where the goal is to envelop cells in an environment mimicking extracellular matrix and mediate processes such as cell proliferation and differentiation. Tissue repair in mature organisms can be crippled because many of the molecular cues present in early development are absent. Peptide sequences (epitopes) can be used to influence specific cell matrix interactions leading to tissue formation. Therefore, providing a synthetic scaffold with epitopes affords the possibility of in vivo tissue regeneration.
Nanofiber networks derived from self-assembling peptide amphiphiles (“PA's”) have been used to mimic bone extracellular matrix and provide a scaffold to direct the differentiation of neural progenitor cells in vitro. PA molecules contain a peptide sequence at one terminus that is hydrophilic relative to the hydrophobic alkyl segment. The PA's charge and amphiphilic nature allows for solubility and promotes self-assembly in aqueous media into long cylindrical structures that are nanometers in diameter and up to microns in length. These supramolecular structures can form fibrous strands because of hydrogen bond formation between the amino acids of adjacent PA molecules. In one case, the β-sheet-forming sequence of LLLAAA together with the hydrophobic alkyl tail's collapse is thought to be the driving force in extended structures, rather than spherical micelles. The high aspect ratio nanofibers form a three-dimensional network trapping water, to create a self-supporting gel that is 99% water by mass. Since the hydrophilic portion of the PA contains charged amino acids and is accessible to the aqueous environment, the self-assembled nanofibers can present a high density of epitopes on the periphery of the nanofibers to interact with cells trapped within. However, to understand scaffold properties in vivo, it is necessary to elucidate the structural degradation and migration of the self-assembled materials postimplantation.